Project description:Background: While electronic cigarette (ECIG) use is rapidly rising, their safety profile remains uncertain. The effects of tobacco cigarette (TCIG) smoke on bronchial airway epithelial gene-expression have provided insights into tobacco-related disease pathogenesis. Understanding the impact of electronic cigarettes (ECIGs) on airway gene-expression could provide insights into their potential long-term health effects. Objectives: We sought to compare the bronchial airway gene-expression profiles of former TCIG smokers now using ECIGs with the profiles of former and current TCIG smokers. Methods: We performed gene-expression profiling of bronchial epithelial cells collected from TCIG smokers not using ECIGs (n=21), former smokers using ECIGs (n=15), and current TCIG smokers not using ECIGs (n=9). We then compared our findings with previous studies of the effects of TCIG use on bronchial epithelium, as well an in vitro model of ECIG exposure. Results: Amongst 3,165 genes whose expression varied between the three study groups (q < 0.05), we identified 468 genes significantly altered in ECIG users relative to former smokers (p < 0.05). 79 of these genes were up or down-regulated concordantly between ECIG and TCIG. We did not detect ECIG-associated gene expression changes in known pathways associated with TCIG usage. Genes downregulated in ECIG users are enriched among the genes most downregulated by exposure of airway epithelium to ECIG vapor in vitro. Conclusions: TCIG exposure was associated with a larger number of airway gene-expression changes than with ECIG exposures. ECIGs induce both distinct and shared patterns of gene expression relative to TCIGs in the bronchial airway epithelium.
Project description:Exposure to electronic cigarette (e-cigarette) aerosol has been linked to a number of health concerns, including DNA damage, elevated oxidative stress, release of inflammatory cytokine, and dysfunctions in epithelial barriers. However, little is known about the effect of exclusive e-cigarette use on expression profiles of exosomal miRNAs, which play critical regulatory roles in many inflammatory responses and disease process including cancer. We aim to compare the exosomal microRNAs expression profile between exclusive e-cigarette users and normal controls without any tobacco product use (non-users). Using blood and urine samples from exclusive e-cigarette users and non-users in the Population Assessment of Tobacco and Health (PATH) Wave 1 study (2013-2014), we examined exosomal microRNAs expression levels through Illumina NextSeq 500/550 sequencing. We identified microRNAs that have significantly higher expression levels in exclusive e-cigarette users than non-users. Gene enrichment analysis of these significant exosomal microRNAs showed their involvement in cancer related pathways, which might indicate a potential elevated risk of cancer among exclusive e-cigarette users.
Project description:Background: E-cigarette popularity is on the rise in youth and young adults, with mounting concerns regarding the long-term safety of these devices. Cell culture and animal models have highlighted the damaging potential of e-cigarettes, but to date there is a lack of data from human lung tissue to corroborate these findings. Methods: Using human lung tissue obtained during a bullectomy in young adults, we performed RNA-sequencing to uncover e-cigarette related changes to the human lung transcriptome. Information on e-cigarette use habits was collected via questionnaire. Findings: Individuals reporting daily e-cigarette use had a reduction in the abundance of mRNA for genes related to extracellular matrix formation and organization, but were enriched mRNA related to cilia function and formation. Genes associated with COPD pathophysiology, including MUC5B and TIMP1, were also affected by e-cigarette use. Interpretation: This first study to perform RNA-sequencing in human lung tissue from relatively young daily e-cigarette users identifies a gene signature that is consistent with an increased risk for future chronic lung disease. Importantly, many of these changes were present in individuals who don’t use traditional cigarettes, suggesting e-cigarette use alone can drive the molecular alterations we identified.
Project description:In the summer of 2019, there was a rise in clusters of adolescents and young adults in the United States reporting to emergency departments with acute respiratory distress related to use of e-cigarette (electronic cigarette) or vaping. The number of patients with e-cigarette or vaping-associated lung injury continued to rise through the summer before peaking in September 2019. Through the efforts of state and federal public health agencies, officials were able to define the condition, identify the relationship of the respiratory injury to tetrahydrocannabinol-containing products, and stem the rise in new cases. In this report, we present a comprehensive review of the clinical characteristics and features of patients with e-cigarette or vaping-associated lung injury and guidelines for patient care and management to inform and navigate clinicians who may encounter these patients in their clinical practice.
Project description:OBJECTIVES:Few studies have examined the prevalence of electronic cigarette use among the inpatient population regardless of the patients' cessation goals. The objectives of this study were to examine the prevalence of electronic cigarette use among counseled tobacco users admitted to 2 academic hospitals. METHODS:Cross-sectional data of hospitalized adult tobacco users who were admitted between January 1, 2015 and December 31, 2015 and who received bedside tobacco cessation counseling from a tobacco treatment service counselor were examined. Demographic and smoking history items were compared as a function of electronic cigarette use using chi-square and independent t tests. Logistic regression was used to test independent associations with electronic cigarette use. RESULTS:Of 2194 hospitalized tobacco users counseled, 22% had used an electronic cigarette. Most of these patients used electronic cigarettes to quit or reduce use of combustible cigarettes. Adjusted odds of electronic cigarette use were higher for females (adjusted odds ratio [AOR] 0.60 for male patients, 95% confidence interval [CI] 0.47-0.76), younger patients (AOR 0.98 for older patients, 95% CI 0.97-0.99), and individuals who initiated tobacco use earlier in life (AOR 0.97 for later smoking initiation, 95% CI 0.95-0.99). CONCLUSIONS:Screening hospitalized cigarette smokers for electronic cigarette use offers an opportunity to counsel all patients on evidence-based quit aids. Young, female patients are most likely to use electronic cigarettes and may benefit most from directed discussions about electronic cigarette use and Federal Drug Administration-approved cessation methods during smoking cessation counseling.
Project description:Importance:Electronic cigarettes (e-cigarettes) have gained unprecedented popularity, but virtually nothing is known about their cardiovascular risks. Objective:To test the hypothesis that an imbalance of cardiac autonomic tone and increased systemic oxidative stress and inflammation are detectable in otherwise healthy humans who habitually use e-cigarettes. Design, Setting, and Participants:Cross-sectional case-control study of habitual e-cigarette users and nonuser control individuals from 2015 to 2016 at the University of California, Los Angeles. Otherwise healthy habitual e-cigarette users between the ages of 21 and 45 years meeting study criteria, including no current tobacco cigarette smoking and no known health problems or prescription medications, were eligible for enrollment. Healthy volunteers meeting these inclusion criteria who were not e-cigarette users were eligible to be enrolled as control individuals. A total of 42 participants meeting these criteria were enrolled in the study including 23 self-identified habitual e-cigarette users and 19 self-identified non-tobacco cigarette, non-e-cigarette user control participants. Main Outcomes and Measures:Heart rate variability components were analyzed for the high-frequency component (0.15-0.4 Hz), an indicator of vagal activity, the low-frequency component (0.04-0.15 Hz), a mixture of both vagal and sympathetic activity, and the ratio of the low frequency to high frequency, reflecting the cardiac sympathovagal balance. Three parameters of oxidative stress were measured in plasma: (1) low-density lipoprotein oxidizability, (2) high-density lipoprotein antioxidant/anti-inflammatory capacity, and (3) paraoxonase-1 activity. Results:Of the 42 participants, 35% were women, 35% were white, and the mean age was 27.6 years. The high-frequency component was significantly decreased in the e-cigarette users compared with nonuser control participants (mean [SEM], 46.5 [3.7] nu vs 57.8 [3.6] nu; P?=?.04). The low-frequency component (mean [SEM], 52.7 [4.0] nu vs 39.9 [3.8] nu; P?=?.03) and the low frequency to high frequency ratio (mean [SEM], 1.37 [0.19] vs 0.85 [0.18]; P?=?.05) were significantly increased in the e-cigarette users compared with nonuser control participants, consistent with sympathetic predominance. Low-density lipoprotein oxidizability, indicative of the susceptibility of apolipoprotein B-containing lipoproteins to oxidation, was significantly increased in e-cigarette users compared with nonuser control individuals (mean [SEM], 3801.0 [415.7] U vs 2413.3 [325.0] U; P?=?.01) consistent with increased oxidative stress, but differences in high-density antioxidant/anti-inflammatory capacity and paraoxonase-1 activity were not significant. Conclusions and Relevance:In this study, habitual e-cigarette use was associated with a shift in cardiac autonomic balance toward sympathetic predominance and increased oxidative stress, both associated with increased cardiovascular risk.
Project description:Background: The microbiome is increasingly being linked to cancer risk. Little is known about the lung and oral cavity microbiomes in healthy smokers (SM), and even less for electronic cigarette (EC) users, compared healthy never-smokers (NS). Methods: In a cross-sectional pilot study of SM (N=8), EC users (N=10) and NS (N=10) saliva and bronchoscopy-collected bronchoalveolar lavage samples were collected. Bacteria species were identified through metatranscriptome profiling by RNA-sequencing to study associations with the lung and oral microbiome. Pairwise comparisons and linear modeling was assessed with false discovery rates <0.1. Results: Total bacterial load was similar for the SM, EC users and NS, and there was no differences in the bacterial diversity across groups. In the lung, there were 44 bacterial species that were statistically significantly different for SM/NS, 80% of which were decreased in the SM. There were 12 bacterial species that were different for SM/EC users, all of which were decreased, 10 of which were also identified in the SM/NS comparison. The 2 bacterial species unique to SM/EC comparison were Neisseria sp. KEM232 and Curvibacter sp. AEP1-3. From the top 5 decreased species in SM/EC, 3 were also identified in the SM/NS comparison (Neisseria elongata, Neisseria sicca, and Haemophilus parainfluenzae) and 2 of these were unique to the SM/EC comparison (Neisseria zoodegmatis and Ottowia sp. oral taxon 894). There were 8 species increased in SM compared to NS, none of which are known to be clinically significant. In the oral microbiome, 152 bacteria species were differentially abundant for the SM/NS analysis, and only 17 for the EC/NS comparison, all which were also present in SM/NS comparisons. There were 21 bacteria that were differentially abundant in both the lung and oral cavity for SM and NS, 95% also were decreased in the SM. Conclusion: Smoking and EC use do not appear to materially affect the lung microbiome, although differences are noted of unclear clinical significance. Most differentially abundant bacteria decreased, which may be due to a toxic effect of cigarette smoke, including a change in humidity or heating. Given the low number of overlapping oral and lung microbes, the oral microbiome does not appear to be a good surrogate for smoking-related effects in the lung.
Project description:Apoptosis of lung epithelial and endothelial cells by exposure to cigarette smoke (CS) severely damages the lung tissue, leading to the pathogenesis of emphysema, but the underlying mechanisms are poorly understood. We have recently established a direct correlation between decreased lipid raft CFTR expression and emphysema progression through increased ceramide accumulation. In the present work, we investigated the role of membrane CFTR in regulating apoptosis and autophagy responses to CS exposure. We report a constitutive and CS-induced increase in the number of TUNEL-positive apoptotic cells in Cftr(-/-) murine lungs compared with Cftr(+/+) murine lungs that also correlated with a concurrent increase in the expression of ceramide, NF-?B, CD95/Fas, lipid raft proteins, and zonula occludens (ZO)-1/2 (P < 0.001). We also verified that stable wild-type CFTR expression in CFBE41o(-) cells controls constitutively elevated caspase-3/7 activity (-1.6-fold, P < 0.001). Our data suggest that membrane CFTR regulates ceramide-enriched lipid raft signaling platforms required for the induction of Fas-mediated apoptotic signaling. In addition, lack of membrane CFTR also modulates autophagy, as demonstrated by the significant increase in constitutive (P < 0.001) and CSE-induced (P < 0.005) perinuclear accumulation of green fluorescent protein-microtubule-associated protein 1 light chain-3 (LC3) in the absence of membrane CFTR (CFBE41o(-) cells). The significant constitutive and CS-induced increase (P < 0.05) in p62 and LC3? expression in CFTR-deficient cells and mice corroborates these findings and suggest a defective autophagy response in the absence of membrane CFTR. Our data demonstrate the critical role of membrane-localized CFTR in regulating apoptotic and autophagic responses in CS-induced lung injury that may be involved in the pathogenesis of severe emphysema.